Apomorphine in Parkinson’s disease

Schwab R, Amador L, Lettvin J. (1951) Apomorphine in Parkinson s disease. Trans Am Neurol Assoc 56 251-253. 

Courty E, Durif F, Zenut M, Courty P, Lavarenne J. Psychiatric and sexual disorders induced by apomorphine in Parkinson s disease. Clin Neuropharmacol 1997 20(2) 140-7. 

Hughes, A.J. Bishop, S. Kleedorfer, B. Turjanski, N. Fernandez, W. Lees, A.J. Stern, G.M. (1993) Subcutaneous apomorphine in Parkinson s Disease Response to chronic administration for up to five years. Movement Disorders 8, 165-170. 

Schwab, R., L. Amador andj. Lettvin, Trans. Am. Neurol. Assoc., 56, 1951, 251-253. (Apomorphine in Parkinson s disease)... 

Corsini G Del Zompo M, Gessa G Mangoni A. (1979) Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson s disease. Lancet 1 954-956. 

Deleu D, Hanssens Y, Northway MG (2004) Subcutaneous apomorphine An evidence-based review of its use in Parkinson s disease. Drugs Aging 21 687-709. 

Haq IU et al Apomorphine therapy in Parkinson s disease A review. Expert Opin Pharmacother 2007 8 2799. [PMID 17956200]... 

Apomorphine, a very potent non-selective dopamine agonist, which acts on both Di and D2 receptors, has been nsed with some snccess in Parkinson s disease, particn-larly in patients with severe long-term adverse effects of levodopa. Because of first-pass metabohsm it has to be used subcutaneously, sublingually, or intranasally. Its adverse effects resemble those of levodopa. 

Manson AJ, Hanagasi H, Turner K, Patsalos PN, Carey P, Ratnaraj N, Lees AJ. Intravenous apomorphine therapy in Parkinson s disease chnical and pharmacokinetic observations. Brain 2001 124(Pt 2) 331 0. 

O Sullivan JD, Hughes AJ. Apomorphine-induced penile erections in Parkinson s disease. Mov Disord 1999 14(4) 701-2. 

Colzi A, Turner K, Lees AJ. Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson s disease. J Neurol Neurosurg Psychiatry 1998 64(5) 573-6. 

The change in structure from morphine to apomorphine profoundly changes its physiological action. The central depressant effects of morphine are much less pronounced, and the stimulant effects are enhanced greatly, thereby producing emesis by a purely central mechanism. It is administered subcutaneously to obtain emesis. It is ineffective orally. Apomorphine is one of the most effective, prompt (10 to 15 minutes), and safe emetics in use today. Care should be exercised in its use. however, bccau.se it may be depressant in already-depressed patients. It is currently cla.ssified as an "orphan drug" for use in Parkinson s disease. 

The dopamine D /D2 receptor agonist R-(-)-apomorphine has proven to be very effective in Parkinson s disease. Subcutaneously administered R-(-)-apomorphine in combination with L-DOPA rapidly and consistently reverses the off period motor deficits.253 256 Beside its action as a dopamine D,/D2 receptor agonist, R-(-)-apomorphine can also act as a radical scavenger257 and, therefore, may have neuroprotective properties. One of the major limitations of the clinical use of R-(-)-apomorphine, a catechol-aporphine, however, is its low oral activity. 

People with Parkinson s disease show a specific degeneration of the nigrostriatal tract so DA must be linked in some way to the control of motor function. It is also known that an imbalance of DA function on the two sides of the rat brain, either by stimulation or lesion of one SN, causes off-line or rotational movement (Ungerstadt and Arbuthnott 1970). This is best shown some days after 6-OHDA lesion of one substantia nigra and its nigrostriatal pathway when systemic apomorphine (DA agonist) causes animals to turn away from the lesioned side (contraversive), presumably... 

Grunblatt E, Mandel S, Maor G, Youdim MB. 2001. Gene e]q>ression analysis in N-methyl-4-phenyl- 1,2,3,6-tetrahydro-pyridine mice model of Parkinson s disease using cDNA microarray effect of R-apomorphine. J Neurochem 78 1. 

Yuan H, Sarre S, Ebinger G, Michotte Y. Neuropro-tective and neurotrophic effect of apomorphine in the striatal 6-OHDA-lesion rat model of Parkinson s disease. Brain Res. 2004 1026 95-107. 

Dopamine - low doses of the dopamine agonist apomorphine increase slow-wave sleep and, like other dopaminometics, cause somnolence in patients with Parkinson s disease. Conversely, dopamine autoreceptor antagonists, which enhance dopamine release, reduce both REM and non-REM sleep. Stimulants such as cocaine cause arousal by activating D2 postsynaptic receptors, effects which are blocked by most neuroleptics. 

Dopamine agonists include bromocriptine, cabergoline, lysuride, pergolide, apomorphine, pramipexole and ropinirole. These drugs are not converted into dopamine but have a direct effect on dopamine receptors in the brain. Dopamine agonists are used both as adjuncts to co-careldopa and co-beneldopa therapy and also initially in early Parkinson s disease, especially in younger adults. 

Apomorphine is a potent dopamine agonist, which is sometimes useful in advanced Parkinson s disease for patients with severe unpredictable off periods on treatment. It is only available as a subcutaneous injection or infusion and thus requires significant patient and/or carer involvement in treatment. It is highly emetogenic so patients must receive domperidone, starting at least 2 days before apomorphine treatment. 

Continuous subcutaneous infusion of apomorphine can transform the quality of life of yoimger patients with severe motor fluctuations and dyskinesia, but this may lead to neuropsychiatric effects. If drug treatment fails in yormg non-demented patients, stereotactic subthalamotomy or bilateral stereotactic subthalamic stimulation can be very successful with only a small risk of surgical complications in experienced hands. Some 20% of patients with Parkinson s disease, notable the older ones, develop impairment of memory and speech with a fluctuating confusional state and hallucinations. As these symptoms are often aggravated by medication, it is... 

A J. Lees, Proceedings ofth e XII International Symposium on Parkinson s Disease Satellite Symposium Apomorphine in the Treatment of Parkinson s Disease, London, March 1997. 

In a placebo-controlled crossover study in 24 patients with Parkinson s disease a single dose of entaeapone 200 mg or 400 mg given 30 minutes before a subcutaneous injeetion of apomorphine had no effeet on the phar-maeokineties of apomorphine. In addition, entaeapone had no effeet on measures of apomorphine effieaey (tapping test and ineidenee of dyskinesias). ... 

Note that prochlorperazine should not be given if apomorphine is used for Parkinson s disease, as its dopamine antagonist actions can worsen the disease (see also Levodopa + Antiemetics , p.682). Because apomorphine is highly emetogenic at the doses required for the treatment of Parkinson s disease (1 to 4 mg/hour by subcutaneous infusion), patients with Parkinson s disease requiring apomorphine should be pretreated with domperidone 20 mg three times daily for at least 2 days. Rare reports of extrapyramidal adverse effects have been reported with ondansetron, which may be of relevance in patients with Parkinson s Disease. 

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